Biological evidence that SOCS-2 can act either as an enhancer or suppressor of growth hormone signaling
- Author(s)
- Greenhalgh, CJ; Metcalf, D; Thaus, AL; Corbin, JE; Uren, R; Morgan, PO; Fabri, LJ; Zhang, JG; Martin, HM; Willson, TA; Billestrup, N; Nicola, NA; Baca, M; Alexander, WS; Hilton, DJ;
- Details
- Publication Year 2002-10-25,Volume 277,Issue #43,Page 40181-40184
- Journal Title
- JOURNAL OF BIOLOGICAL CHEMISTRY
- Publication Type
- Journal Article
- Abstract
- Suppressor of cytokine signaling (SOCS)-2 is a member of a family of intracellular proteins implicated in the negative regulation of cytokine signaling. The generation of SOCS-2-deficient mice, which grow to one and a half times the size of their wild-type littermates, suggests that SOCS-2 may attenuate growth hormone (GH) signaling. In vitro studies indicate that, while SOCS-2 can inhibit GH action at low concentrations, at higher concentrations it may potentiate signaling. To determine whether a similar enhancement of signaling is observed in vivo or alternatively whether increased SOCS-2 levels repress growth in vivo, we generated and analyzed transgenic mice that overexpress SOCS-2 from a human ubiquitin C promoter. These mice are not growth-deficient and are, in fact, significantly larger than wild-type mice. The overexpressed SOCS-2 was found to bind to endogenous GH receptors in a number of mouse organs, while phosphopeptide binding studies with recombinant SOCS-2 defined phosphorylated tyrosine 595 on the GH receptor as the site of interaction. Together, the data implicate SOCS-2 as having dual effects on GH signaling in vivo.
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- Keywords
- MAMMARY-GLAND DEVELOPMENT; MICE LACKING SUPPRESSOR; NEGATIVE REGULATION; TRANSGENIC MICE; CYTOKINE; RECEPTOR; EXPRESSION; INHIBITION; STAT5B; TRANSDUCTION
- Publisher's Version
- https://doi.org/10.1074/jbc.C200450200
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- Refer to copyright notice on published article.
Creation Date: 2002-10-25 12:00:00